Impact of Patients' Income on Stroke Prognosis.
For patients diagnosed with stroke, the association between socioeconomic status and patient outcomes is poorly understood. Our objective was to define the impact of patients' socioeconomic status on their prognosis after stroke in the United States. Utilizing the Nationwide Inpatient Sample, we identified discharges involving a diagnosis of stroke from 2008 to 2013. Cohort was dichotomized to low-income patients (L-patients) and not-low-income patients (NL-patients). Z-test statistic was used to test the impact of income on stroke outcome. The reported annual total in-hospital mortality for L-patients and NL-patients diagnosed with stroke at U.S. hospitals decreased significantly during the study period (P < .001). The mortality of L-patients decreased significantly from 1759 (4.16%) to 955 (2.54%) during study period. Similarly, NL-patients' mortality decreased significantly from 4818 (4.52%) to 2300 (2.47%) during the same period. The difference between the annual total in-hospital mortality for L-patients and NL-patients due to stroke was statistically significant throughout the entire study period (P < .0001). Notably, from 2008 to 2013, the annual total routine discharges, annual total discharges to short-term hospital, annual total discharges to another institution, and annual total discharges to home health care were statistically significantly different between the 2 populations of patients (P < .0001). Socioeconomic status has an impact on patient outcome after treatment of stroke in hospitals in the United States. Further study is needed to investigate the etiology of these differences between patients' socioeconomic status and their clinical outcomes after stroke.


Enriched endogenous n-3 polyunsaturated fatty acids alleviate cognitive and behavioral deficits in a mice model of Alzheimer's disease.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accompanied by memory deficits and neuropsychiatric dysfunction. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have seemly therapeutic potential in AD, but the benefit of n-3 PUFAs is still in debates. Here, we employed a transgenic mice carry fat-1 gene to encode n-3 desaturase from Caenorhabditis elegans, which increase endogenous n-3 PUFAs by converting n-6 PUFAs to n-3 PUFAs crossed with amyloid precursor protein (APP) Tg mice to evaluate the protective effects of endogenous n-3 PUFAs on cognitive and behavioral deficits of APP Tg mice. We fed APP, APP/fat-1 and fat-1 mice with n-6 PUFAs rich diet. Brain tissues were collected at 3, 9 and 12 months for fatty acid and gene expression analysis, histology and protein assays. Morris Water Maze Test, open field test and elevated plus maze test were performed to measure the behavior capability. From the results, the expression of fat-1 transgene increased cortical n-3: n-6 PUFAs ratio and n-3 PUFAs concentrations, and sensorimotor dysfunction and cognitive deficits in AD were significantly less severe in APP/fat-1 mice with endogenous n-3 PUFAs than in APP mice controls. The protection against disturbance of spontaneous motor activity and cognitive deficits in AD was strongly correlated with increased n-3: n-6 PUFAs ratio and endogenous n-3 PUFAs, reduced APP generation, inhibited amyloid β peptide aggregation, suppressed nuclear factor-kappa B and astroglia activation, and reduced death of neurons in the cortex of APP/fat-1 mice compared with APP mice controls. In conclusion, our study demonstrates that an available medication with the maintenance of enriched n-3 PUFAs in the brain could slow down cognitive decline and prevent neuropsychological disorder in AD.


Evolution and implementation of radiographic response criteria in neuro-oncology.
Radiographic response assessment in neuro-oncology is critical in clinical practice and trials. Conventional criteria, such as the MacDonald and response assessment in neuro-oncology (RANO) criteria, rely on bidimensional (2D) measurements of a single tumor cross-section. Although RANO criteria are established for response assessment in clinical trials, there is a critical need to address the complexity of brain tumor treatment response with multiple new approaches being proposed. These include volumetric analysis of tumor compartments, structured MRI reporting systems like the Brain Tumor Reporting and Data System, and standardized approaches to advanced imaging techniques to distinguish tumor response from treatment effects. In this review, we discuss the strengths and limitations of different neuro-oncology response criteria and summarize current research findings on the role of novel response methods in neuro-oncology clinical trials and practice.


The biochemical characterization of a cell surface antigen associated with acute lymphoblastic leukemia and lymphocyte precursors.
The acute lymphoblastic leukemia- (ALL) associated membrane antigen is a single glycosylated polypeptide of approximate m.w. of 100,000 (gp100), containing no intrachain disulfide linkages. Approximately 50% of gp100 will bind to lentil lectin, whereas 100% will bind to the lectin from Ricinus communis. Both lentil-binding and lentil nonbinding forms of the antigen appear to be identical by 2-dimensional isoelectric focusing/SDS polyacrylamide gel electrophoresis and peptide mapping. Carbohydrate, although contributing approximately 20 to 25% of the m.w., appears not to be involved in the antigenic site of the ALL antigen as judged by precipitation of a molecule after tunicamycin treatment of cells or glycosidase digestion. Charge shift electrophoresis and labeling with the lipophilic nitrene reagent hexanoyl diiodo-N-(4-azido-2-nitrophenyl)-tyramine suggests that the cALL antigen is probably not an integral membrane protein; however, it remains tightly bound to the plasma membrane after subcellular fractionation. A glycoprotein of the same m.w. has been detected by immunoprecipitation on bone marrow cells of nonleukemic patients. serologic studies indicate that the cALL-associated antigen is found on the terminal transferase-positive lymphoid cells, and it therefore seems likely that the gp100 molecule is a normal gene products of lymphocyte precursors.


[Exogenous HBx promotes epithelial-mesenchymal transition of hepatic progenitor cells in Kunming mice].
Objective To construct an animal model in which hepatitis B virus X protein (HBx) directly affect hepatic progenitor cells (HPCs), and investigate the potential mechanisms underlying epithelial-mesenchymal transition (EMT) of HPCs. Methods Kunming mice were given 2 mL/L carbon tetrachloride (CCL4) in oil solution by gavage twice a week. Four weeks later, HPCs transfected with recombinant lentiviral vectors stably expressing HBx gene as well as empty vectors were separately injected into the mice via the portal vein, and at the same time, the mice underwent a partial hepatectomy. The gavage twice a week continued after the operation. And on days 3, 5, 7, 14, 21 28 postoperation, the mice were sacrificed and the livers were removed. Fluorescence quantitative PCR was used to detect the mRNA expression level of HBx; immunohistochemistry was performed to observe the exogenous cell survival in vivo. The expression levels of E-cadherin, N-cadherin, vimentin and CK18 were assessed by fluorescence quantitative PCR and Western blotting. Results Immunohistochemistry showed that the exogenous cells obviously survived in vivo in the postoperative liver tissues. Moreover, the expression of HBx was enhanced and expanded over time. Fluorescence quantitative PCR and Western blotting showed that overexpressed HBx downregulated the expressions of E-cadherin and CK18, while upregulated the expressions of N-cadherin and vimentin. Conclusion HBx plays an important role in the regulation of EMT of HPCs in vivo.


Comparison of culture and a multiplex probe PCR for identifying Mycoplasma species in bovine milk, semen and swab samples.
Mycoplasma spp. are a major cause of mastitis, arthritis and pneumonia in cattle, and have been associated with reproductive disorders in cows. While culture is the traditional method of identification the use of PCR has become more common. Several investigators have developed PCR protocols to detect M. bovis in milk, yet few studies have evaluated other sample types or other important Mycoplasma species. Therefore the objective of this study was to develop a multiplex PCR assay to detect M. bovis, M. californicum and M. bovigenitalium, and evaluate its analytical performance against traditional culture of bovine milk, semen and swab samples. The PCR specificity was determined and the limit of detection evaluated in spiked milk, semen and swabs. The PCR was then compared to culture on 474 field samples from individual milk, bulk tank milk (BTM), semen and swab (vaginal, preputial, nose and eye) samples. Specificity analysis produced appropriate amplification for all M. bovis, M. californicum and M. bovigenitalium isolates. Amplification was not seen for any of the other Mollicutes or eubacterial isolates. The limit of detection of the PCR was best in milk, followed by semen and swabs. When all three Mycoplasma species were present in a sample, the limit of detection increased. When comparing culture and PCR, overall there was no significant difference in the proportion of culture and PCR positive samples. Culture could detect significantly more positive swab samples. No significant differences were identified for semen, individual milk or BTM samples. PCR identified five samples with two species present. Culture followed by 16S-23S rRNA sequencing did not enable identification of more than one species. Therefore, the superior method for identification of M. bovis, M. californicum and M. bovigenitalium may be dependent on the sample type being analysed, and whether the identification of multiple target species is required.


Generation of optical 3D unpolarized lattices in a tightly focused random beam.
We study the three-dimensional (3D) polarization properties of a tightly focused partially coherent vector beam whose initial spatial coherence structure exhibits a lattice distribution. By examining the 3D degree of polarization and the polarimetric dimension of the tightly focused field, we demonstrate that this initial spatial coherence structure induces a 3D isotropically unpolarized beam lattice in the focal plane. Along the longitudinal direction, we observe the formation of nearly 3D unpolarized channels spanning 16 wavelengths in length near the focal region. We demonstrate that the spatial distribution of the 3D unpolarized lattice can be conveniently controlled through engineering the spatial coherence structure of the incident beam.


Visualization Analysis of Research Trends and Hotspots in Inspiratory Muscle Training.
BACKGROUND Inspiratory muscle training (IMT) aims to train inspiratory muscles based mainly on the diaphragm by applying a load resistance during the inspiratory process. Many papers related to IMT have been published in various journals; however, no articles objectively and directly present the development trends and research hotspots of IMT. Therefore, this study used CiteSpace to visually analyze recent IMT-related publications to provide valuable information for future IMT-related studies. MATERIAL AND METHODS CiteSpace was applied to analyze the IMT-related publications by countries, institutions, journals, authors, references, and keywords. RESULTS We included 504 papers. The number of IMT-related publications trended upward between 2009 and 2022. Leuven had the highest number of publications by an institution. The American Journal of Respiratory and Critical Care Medicine was the most frequently co-cited journal. Half of the top 10 references cited were from Journal Citation Reports (JCR) Q1 and half were about the application of IMT in chronic obstructive pulmonary disorder. Gosselink was the author with the highest number of publications and Aldrich was the author with the highest co-citation frequency. The preponderance of studies on the surgical population and postoperative pulmonary complications reflects potential application of IMT in enhanced recovery after surgery. CONCLUSIONS This study provides scholars with important information related to IMT research. It analyzes IMT research trends and status, which can help researchers identify primary topics in the field and find ways to explore new research directions to promote the application of IMT in clinical practice and the cooperation of IMT-related disciplines.


Novel O-superfamily conotoxins identified by cDNA cloning from three vermivorous Conus species.
The O-superfamily of conotoxins includes several subfamilies with different pharmacological targets, all of which are voltage-gated ion channels and distributed widely in varied Conus species. The venom components from any Conus species are quite distinct from those of other species. Seven novel O-superfamily peptides were identified by cDNA cloning from the three vermivorous Conus species of C. betulinus, C. lividus and C. caracteristicus native to Hainan. They share three common signal sequences, and a conserved arrangement of cysteine residues (C-C-CC-C-C). Phylogenetic analysis of newly found conotoxins in this study and known homologue O-superfamily sequences from the other Conus species was performed systematically. Divergence and percentage identity of the amino acid sequences of the signal regions suggest that the novel conotoxins described in this investigation belong to the three broad clades: MSGL, ME-QK and MKLT, each of which has its own characteristic signature signal sequence and cysteine codon conservation. Relative to this work, it is noted that O-superfamily conotoxins are not well represented from vermivorous species. The elucidated cDNAs of these newly found vermivorous toxins would facilitate a better understanding for basic research and drug discovery.


On the exponent in the power law for the attenuation at low frequencies in sandy sediments.
Shallow water transmission loss measurements yield intrinsic attenuation estimates for acoustic waves in the underlying sediment, with results that are consistent with attenuation being proportional to frequency raised to a power n, with n between 1.6 and 1.87. Plausible theory suggests that n should be identically 2. The discrepancy can be explained because the inverse analysis inferences were made with the neglect of an additional attenuation mechanism where generated lower velocity shear waves carry energy downwards out of the waveguide. The shear wave effect has a weaker dependence on frequency than the intrinsic attenuation, so the apparent exponent is shifted downward.


High coronary heart disease rates among Dutch women of the baby boom, born 1945-1959: age-cohort analysis and projection.
After a steep decline in older generations, coronary heart disease mortality is stagnating in female cohorts born after the Second World War. We analysed past trends and predicted future health care needs for coronary heart disease in the Dutch population. A loglinear age-cohort model relates numbers of deaths and hospital admissions for coronary heart disease to sex, age, birth cohort and population size, and projects age-cohort changes over the future population. Population size, population forecasts and coronary heart disease mortality (period 1970-1999) are from vital statistics. Numbers of hospitalised acute coronary events are from the nationwide hospital register (period 1980-1999). Among men, the rate ratios of deaths and hospital admissions were, respectively, 0.21 (death) and 0.78 (survivors at discharge) in the cohorts born in the period 1948-1962 compared to the period 1918-1922. Among women, the same rate ratios were 0.41 and 1.89. The projection model predicts 22% less deaths from coronary heart disease and 22% more survivors of an infarction in 2015, among men. Among women, there will be 5% less deaths and 70% more survivors of an infarction, most of these being middle age members of the baby boom cohorts. Stagnating all-cause mortality is correlated with an upward trend in coronary heart disease risk in the female baby boomers. Heart health care needs among middle-aged women will increase sharply. These changes are correlated to high lung cancer mortality and high smoking rates in these cohorts.


Ionicity in disordered GeSe2: a comparison of first-principles and atomistic potential models.
The structural properties of liquid GeSe(2), generated using two distinct computational methodologies, are compared. The results of molecular dynamics simulations, utilizing both first-principles density functional and a potential model which account for aspects of many-body interactions, are considered. The potential model favors ionic character in the bonding, resulting in a structure with very little chemical disorder and no homopolar bonds, in contrast to experimental observation. The use of a relatively simple potential model is shown to be useful in order to understand differences between the observed experimental structure and those obtained from the first-principles approach, the latter being affected by insufficient account of ionic character in the bonding. Both computational schemes are able to predict the appearance of the first sharp diffraction peak in the total neutron structure factor and in some of the partial structure factors as well as the concomitant presence of corner- and edge-sharing tetrahedral connections. For the potential model, this holds true provided the system temperatures are set to values high enough to allow for diffusion properties typical of a liquid. Structural properties obtained for the two sets of configurations are in closer agreement when the potential model is applied at very high temperatures.


Nonadherence with mood stabilizers: prevalence and predictors.
The prevalence of nonadherence with mood stabilizers ranges from about 18% to 52%. Only 1% of publications on mood stabilizers address this issue. This study aimed to explore the prevalence and predictors of nonadherence in a cohort of individuals with affective disorders receiving long-term treatment with mood stabilizers. Subjects receiving lithium, carbamazepine, and/or valproate were identified from biochemistry laboratory data. Ninety-eight of these subjects had major depressive disorder (N = 20) or bipolar disorder (N = 78) (DSM-IV) and gave informed consent to participate in a structured clinical interview to assess their medication adherence and the factors that influenced it. Just under 50% of subjects (46/98) acknowledged some degree of medication nonadherence in the previous 2 years, and 32% (29/92) reported only partial adherence in the last month (missing 30% or more of their prescribed medication). Backward stepwise logistic regression demonstrated that partially adherent subjects were best distinguished from adherent subjects by a more frequent past history of nonadherence, denial of severity of illness, and greater duration of being prescribed a mood stabilizer. Rates of mood stabilizer nonadherence are high. Attitudes and behaviors are better predictors of nonadherence than side effects from medication. Clinicians need to inquire routinely about problems with adherence.


Variants in HNRNPDL and SETX Not Necessarily Indicate Familial Amyotrophic Lateral Sclerosis or Limb Girdle Muscular Dystrophy 1G in Acute Muscular Respiratory Failure.
Genetic work-up is useful for the identification of a primary myopathy. However, even sophisticated genetic methods may fail to detect the underlying cause of myopathy as in the following case. The patient is a 52-year-old female with a history of epilepsy, arterial hypertension, atrial flutter requiring cardioversion, ablation, and anticoagulation, coronary heart disease, hyperlipidemia, and hyper-CKemia. At age 52 years, she was referred for heart failure due to ischemic cardiomyopathy requiring appropriate medication and implantation of an ICD. During hospitalization she developed acute muscular respiratory failure requiring mechanical ventilation. Genetic panels for myopathy, neuropathy, and cardiomyopathy revealed variants of unknown significance in the HNRNPDL and SETX genes respectively. Clinical presentation and muscle biopsy, however, suggested metabolic myopathy. Acute muscular respiratory failure may require traditional diagnostic work-up for primary myopathy and long-term invasive and non-invasive ventilation. Panel investigations not necessarily lead to a conclusive diagnosis. The multisystem nature of the condition rather suggests a metabolic defect than LGMD-1G or fALS as genetic findings suggested.


Hurricane Sandy Exposure and the Mental Health of World Trade Center Responders.
The psychological consequences of a second disaster on populations exposed to an earlier disaster have rarely been studied prospectively. Using a pre- and postdesign, we examined the effects of Hurricane Sandy on possible World Trade Center (WTC) related posttraumatic stress disorder (PTSD Checklist score of ≥ 50) and overall depression (major depressive disorder [MDD]; Patient Health Questionnaire depression score of ≥ 10) among 870 WTC responders with a follow-up monitoring visit at the Long Island WTC Health Program during the 6 months post-Hurricane Sandy. The Hurricane Sandy exposures evaluated were damage to home (8.3%) and to possessions (7.8%), gasoline shortage (24.1%), prolonged power outage (42.7%), and filing a Federal Emergency Management Agency claim (11.3%). A composite exposure score also was constructed. In unadjusted analyses, Hurricane Sandy exposures were associated with 1.77 to 5.38 increased likelihood of PTSD and 1.58 to 4.13 likelihood of MDD; odds ratios for ≥ 3 exposures were 6.47 for PTSD and 6.45 for MDD. After adjusting for demographic characteristics, WTC exposure, pre-Hurricane Sandy mental health status, and time between assessments, reporting ≥ 3 Hurricane Sandy exposures was associated with a 3.29 and 3.71 increased likelihood of PTSD and MDD, respectively. These findings underscore the importance of assessing the impact of a subsequent disaster in ongoing responder health surveillance programs.


Modification of De Vega's tricuspid annuloplasty for experimental tricuspid regurgitation.
We propose a new experimental model of tricuspid annular dilatation and provide some modifications to De Vega's tricuspid annuloplasty to treat this condition. Tricuspid annular dilatation was done by creating ten 1.5-mm incisions around the circumference of the tricuspid annulus. The annulus became significantly dilated from 7.6 cm to 9.4 cm (p < 0.01). After dilatation, 2-0 polypropylene stitches were placed circumferentially around the tricuspid annulus and the suture ends were brought outside the heart through the right atrial wall. After cardiac resuscitation, the following hemodynamic variables were measured as preload was increased incrementally: mean right atrial pressure, v wave of atrial pressure, right ventricular end-diastolic pressure, and cardiac output. Measurements were obtained and preload-output curves were constructed for three time periods: before annular dilatation (Control); after dilatation, but before external adjustment (Before); and after external modification of the annulus (After). Following cardiac resuscitation, right atrial and ventricular pressures were significantly higher after annular dilatation, compared to control values. The preload-output curve was shifted to the right, and cardiac output could not be increased above 0.9 L/min. Once the extracardiac adjustment was accomplished, these pressures were returned to control values, and the preload-output relationship was returned to normal curve.


Chronic escitalopram treatment caused dissociative adaptation in serotonin (5-HT) 2C receptor antagonist-induced effects in REM sleep, wake and theta wave activity.
Several multi-target drugs used in treating psychiatric disorders, such as antidepressants (e.g. agomelatine, trazodone, nefazodone, amitriptyline, mirtazapine, mianserin, fluoxetine) or most atypical antipsychotics, have 5-hydroxytryptamine 2C (5-HT2C) receptor-blocking property. Adaptive changes in 5-HT2C receptor-mediated functions are suggested to contribute to therapeutic effects of selective serotonin reuptake inhibitor (SSRI) antidepressants after weeks of treatment, at least in part. Beyond the mediation of anxiety and other functions, 5-HT2C receptors are involved in sleep regulation. Anxiety-related adaptive changes caused by antidepressants have been studied extensively, although sleep- and electroencephalography (EEG)-related functional studies are still lacking. The aim of this study was to investigate the effects of chronic SSRI treatment on 5-HT2C receptor antagonist-induced functions in different vigilance stages and on quantitative EEG (Q-EEG) spectra. Rats were treated with a single dose of the selective 5-HT2C receptor antagonist SB-242084 (1 mg/kg, i.p.) or vehicle at the beginning of passive phase following a 20-day-long SSRI (escitalopram; 10 mg/kg/day, osmotic minipump) or VEHICLE pretreatment. Fronto-parietal electroencephalogram, electromyogram and motility were recorded during the first 3 h of passive phase. We found that the chronic escitalopram pretreatment attenuated the SB-242084-caused suppression in rapid eye movement sleep (REMS). On the contrary, the 5-HT2C receptor antagonist-induced elevations in passive wake and theta (5-9 Hz) power density during active wake and REMS were not affected by the SSRI. In conclusion, attenuation in certain, but not all vigilance- and Q-EEG-related functions induced by the 5-HT2C receptor antagonist, suggests dissociation in 5-HT2C receptor adaptation.


Culture of cancer spheroids and evaluation of anti-cancer drugs in 3D-printed miniaturized continuous stirred tank reactors (mCSTRs).
Cancer continues to be a leading cause of mortality in modern societies; therefore, improved and more reliablein vitrocancer models are needed to expedite fundamental research and anti-cancer drug development. Here, we describe the use of a miniaturized continuous stirred tank reactor (mCSTR) to first fabricate and mature cancer spheroids (i.e. derived from MCF7 cells, DU145 cells, and a mix of MCF7 cells and fibroblasts), and then to conduct anti-cancer drug assays under continuous perfusion. This 3 ml mCSTR features an off-center agitation system that enables homogeneous chaotic laminar mixing at low speeds to support cell aggregation. We incubated cell suspensions for 3 d in ultra-low-attachment plates to allow formation of discoid cell aggregates (∼600µm in diameter). These cell aggregates were then transferred into mCSTRs and continuously fed with culture medium. We characterized the spheroid morphology and the expression of relevant tumor biomarkers at different maturation times for up to 4 weeks. The spheroids progressively increased in size during the first 5-6 d of culture to reach a steady diameter between 600 and 800µm. In proof-of-principle experiments, we demonstrated the use of this mCSTR in anti-cancer drug testing. Three drugs commonly used in breast cancer treatment (doxorubicin, docetaxel, and paclitaxel) were probed at different concentrations in MCF7-derived spheroids. In these experiments, we evaluated cell viability, glucose consumption, spheroid morphology, lactate dehydrogenase activity, and the expression of genes associated with drug resistance (ABCB1andABCC1) and anti-apoptosis (Bcl2). We envision the use of this agitated system as a tumor-on-a-chip platform to expedite efficacy and safety testing of novel anti-cancer drugs and possibly in personalized medicine applications.


Efficacy of instrumentation techniques and irrigation regimens in reducing the bacterial population within root canals.
The purpose of this study was to compare the in vitro intracanal bacterial reduction produced by using two instrumentation techniques and different irrigation methods. Root canals inoculated with Enterococcus faecalis were prepared by using the following techniques and irrigants: alternated rotary motions (ARM) technique, hand nickel-titanium files and 2.5% sodium hypochlorite (NaOCl) as irrigant; ARM technique and combined irrigation with 2.5% NaOCl and citric acid; ARM technique and combined irrigation with 2.5% NaOCl and 2% chlorhexidine gluconate; and Greater Taper rotary files, using 2.5% NaOCl as irrigant. Controls were instrumented by using the ARM technique and irrigated with sterile saline. Canals were sampled before and after preparation. After serial dilution, samples were plated onto Mitis-Salivarius agar, and the colony forming units that were grown were counted. All test techniques and solutions significantly reduced the number of bacterial cells within the root canal (p < 0.05). There was no significant difference between the experimental groups (p > 0.05). Nonetheless, all of them were significantly more effective than the control group (p < 0.05). These findings support the importance of using antimicrobial irrigants during the chemomechanical preparation, regardless of the solutions or instrumentation techniques used.


Medaka piwi is essential for primordial germ cell migration.
Piwi controls the number of primordial germ cells (PGCs) via protecting maternal mRNA from decay and adult germ stem cell division in Drosophila. In mouse and zebrafish, piwi controls maintenance and differentiation of adult germ stem cell during gametogenesis. Whether piwi plays a role in PGC development of vertebrates remains unsolved. We addressed this issue by using medaka (Oryzias latipes) as a vertebrate model. Molecular cloning, sequence comparison and analyses of genomic organization and chromosome synteny led to the identification in this fish of a single piwi gene, called Opiwi. By RT-PCR analyses and in situ hybridization, the Opiwi transcript is maternally supplied and becomes restricted to PGCs and the central nervous system (CNS). Opiwi knockdown did not prevent PGC formation even in the absence of any somatic structures but did significantly reduce the number of PGCs in vivo and in vitro and affect the distribution of PGCs in developing embryos. Surprisingly, depletion of zygotic Opiwi severely and specifically affected PGC migration. We conclude that Opiwi is required not only for determining the PGC number but also for controlling PGC migration. Our results demonstrate that piwi plays a generally conserved role in germ cell development from Drosophila to vertebrate and a specific role in PGC migration.


Myostatin and its association with abdominal obesity, androgen and follistatin levels in women with polycystic ovary syndrome.
What is the role of myostatin and its relationship with obesity, androgens and follistatin levels in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWERS: The myostatin level was positively correlated to the risk of abdominal obesity, but negatively associated with circulating levels of dehydroepiandrosterone sulfate (DHEAS) and follistatin in women with PCOS. Myostatin is a well-known negative regulator of skeletal muscle and is involved in metabolism; however, little is known about the role of myostatin in women with PCOS. In this study, we found that the myostatin level was positively related to the risk of abdominal obesity, but negatively related to the circulating levels of DHEAS and follistatin in women with PCOS. Such a relationship might imply a potential regulatory role of androgens and follistatin in the metabolism of skeletal muscle in women with PCOS. A cross-sectional case-control study. A total of 239 untreated, consecutive women with PCOS and 38 healthy volunteer women without PCOS were enrolled and studied in a tertiary medical center. Myostatin level was higher in women with PCOS than those without PCOS (16.6±15.6 and 14.2±9.7, P=0.025), but were not significantly different between non-obese women with and without PCOS after considering the effect of obesity (P=0.09). Stepwise multivariate regression analysis in women revealed that only the presence of PCOS (β=0.256, P=0.0001), total testosterone (β=0.159, P=0.031), DHEAS (β=-0.188, P=0.0003) and follistatin (β=-0.171, P=0.0001) levels were left in the final model and were significantly related to the myostatin level after considering all the explanatory variables. By using stepwise multivariate regression analysis, the total testosterone levels (β=0.196, P=0.003) were positively, but the DHEAS (β=-0.196, P<0.0001) and follistatin (β=-0.151, P=0.0001) levels were negatively, related to myostatin levels in women with PCOS after adjustment for age, anthropometric measurements, insulin sensitivity index and hormonal profiles. The high myostatin level was associated with the increased risk of abdominal obesity after further adjusting the androgens and follistatin levels in women with PCOS. This study is a cross-sectional case-control design, and therefore, cannot answer the cause-effect relationship among the androgens, follistatin and myostatin levels. The small sample size and non-obese control group may also limit the application of the conclusion of the present study to general population other than women with PCOS. In addition, lack of data regarding muscle mass is another limitation in this study that prevents clarification of the relationship between myostatin, lean mass and obesity and therefore restricts the clinical application of the results. Future studies to investigate the efficacy of exercise and lifestyle modification in treating women with PCOS should consider the myostatin, follistatin and androgen levels as well as the effect of muscle mass and BMI. This study was supported by grants NSC97-2314-B002-079-MY3, NSC98-2314-B002-105-MY3 and NSC 100-2314-B002-027-MY3 from the National Science Council of Taiwan. There is no competing interest declared in this study.


Modelling Structure Activity Landscapes with Cliffs: a Kernel Regression-Based Approach.
Quantitative Structure-Activity Relationship (QSAR) models are increasingly used in hazard and risk assessment. Even when models with linear relationships between activity and a small number of descriptors are built and validated regarding predictivity and statistical assumptions, similar structures can exhibit large differences in activity known as similarity paradoxes or activity cliffs. In order to reduce the impact that similarity paradoxes can have on predictions we have devised a statistical method based on Nadaraya-Watson kernel regression. According to our method, activity cliffs filter out contributions of neighbouring chemicals especially along the cliff axis. Our method decreases density-based certainty in particular for chemicals with strong prediction errors and the implementation of Structure-Activity Landscape Index (SALI) curves shows that our method improves the prediction of activity cliff ranks. We also provide useful indications on the density-based applicability domain and the reliability of individual predictions.


Gastroschisis Trends and Ecologic Link to Opioid Prescription Rates - United States, 2006-2015.
Prevalence of gastroschisis, a serious birth defect of the abdominal wall resulting in some of the abdominal contents extending outside the body at birth, has been increasing worldwide (1,2). Gastroschisis requires surgical repair after birth and is associated with digestive and feeding complications during infancy, which can affect development. Recent data from 14 U.S. states indicated an increasing prevalence of gastroschisis from 1995 to 2012 (1). Young maternal age has been strongly associated with gastroschisis, but research suggests that risk factors such as smoking, genitourinary infections, and prescription opioid use also might be associated (3-5). Data from 20 population-based state surveillance programs were pooled and analyzed to assess age-specific gastroschisis prevalence during two 5-year periods, 2006-2010 and 2011-2015, and an ecologic approach was used to compare annual gastroschisis prevalence by annual opioid prescription rate categories. Gastroschisis prevalence increased only slightly (10%) from 2006-2010 to 2011-2015 (prevalence ratio = 1.1, 95% confidence interval [CI] = 1.0-1.1), with the highest prevalence among mothers aged <20 years. During 2006-2015, the prevalence of gastroschisis was 1.6 times higher in counties with high opioid prescription rates (5.1 per 10,000 live births; CI = 4.9-5.3) and 1.4 times higher where opioid prescription rates were medium (4.6 per 10,000 live births; CI = 4.4-4.8) compared with areas with low prescription rates (3.2 per 10,000 live births; CI = 3.1-3.4). Public health research is needed to understand factors contributing to the association between young maternal age and gastroschisis and assess the effect of prescription opioid use during pregnancy on this pregnancy outcome.


PLGA (85:15) nanoparticle based delivery of rL7/L12 ribosomal protein in mice protects against Brucella abortus 544 infection: A promising alternate to traditional adjuvants.
There is a compelling need for the development of suitable adjuvants for human use to enhance the efficacy of the upcoming vaccines for the prevention of life threatening infections. In the current study, we have tried to explore the immunogenic potential of nanoparticles (NPs) made of PLGA (poly lactic-co-glycolic acid), a biodegradable and biocompatible polymer approved by FDA for human use after entrapping rL7/L12 protein, an immunodominant antigen of Brucella. Adjuvant properties were exhibited by the formulation as it elicited high IgG antibody titers just after first immunization which increased significantly after the booster administration. A good elicitation of the Th1 cytokines especially IFN-γ was recorded. Amongst the IgG antibody subclasses, IgG1 remained the predominant subclass to be elicited in mice serum after immunization; however IgG1/2a ratio showed a mixed profile of Th1/Th2 response. Lymphocyte proliferation assay as a marker of amplification in cellular immunity demonstrated that the splenocytes of the immunized mice had a high proliferation index with reference to the control, revealing that L7/L12 entrapping PLGA nanoparticles are potent inducer of inflammatory cell response indispensable to combat Brucella infection. Enumeration of splenic CFU after 14 days of infection with Brucella abortus 544 showed a significant reduction in log CFU of splenic bacteria in the vaccinated mice as compared to the control group. Therefore it is evident that PLGA nano formulations delivering the entrapped vaccine candidate in mice elicit specific humoral as well as cellular responses specific to the entrapped Brucella antigen. So there is much promise in this approach and this work by highlighting the adjuvant properties of the PLGA nanospheres will accelerate the development of improved vaccines safe for human as well as veterinary use.


Density of os calcis and limb dominance.
The absolute density of the right and left os calcis has been measured in a group of healthy, sedentary volunteers. There was a significant difference between the density of the right and left os calcis in 90% of the subjects. Statistically, when all of the subjects were considered, the side on which the os calcis was denser was also the side of hand preference. Since there was no evidence, in the present study, of the environment having encouraged the use of one foot rather than the other, it is concluded that the concordance between upper limb dominance and greater density of the ipsilateral os calcis must have been determined before birth.


[Further recognition and improvement of multimodality treatment for advanced gastric cancer].
Gastric cancer is one of the most common malignancies in China, which remains in high incidence and mortality. At present, radical surgery remains the cornerstone of multidisciplinary treatment in advanced gastric cancer, but is not the only one. In order to improve prognosis, it is necessary for surgeons to realize and emphasize the idea of comprehensive treatment. Accurate preoperative TNM staging is a prerequisite for selecting reasonable therapeutic modality. Based on standard surgery, multimodal treatments involving (neo-) adjuvant chemotherapy, radiotherapy or molecular target agents still need to be optimized for the best oncologic outcome with minimal morbidities. As to metastatic and late cases, personalized strategy is being acknowledged to prolong survival time and improve quality of life. A deeper understanding of high heterogeneity and biological characteristics of gastric cancer should be carried out, and multidisciplinary team collaboration is quite important to achieve an optimal treatment mode both standardized and individualized, which will benefit every patient.


[Allergic rhinitis, respiratory obstruction and bronchial asthma in the Vienna population].
In the present study the incidence of bronchial asthma, airway complaints, and allergic rhinitis was investigated in a randomized population section including 3000 male and female inhabitants of Vienna (sex ratio 1:1), aged 20-44. Data on complaints in the respiratory tract were obtained from a total of 71% of the study population. Our results suggest that 14.7% of the entire population was suffering from allergic rhinitis (16.4% male versus 13.0% female; p < 0.05). Airway complaints such as wheezing, whistling, and feeling of tightness in the chest, awakening because of shortness of breath or cough were frequently reported, with no major differences between male and female subjects. The overall percentage of study subjects stating that they had suffered from airway complaints in the year before, i.e., the percentage of those giving affirmative answers to one of the questions, was 29%. Bronchial asthma was calculated to be present in 5.1% of the entire population (5.9 male versus 4.4 female). Attacks of asthma were reported by only 2.2% of the subjects, which gives an indication of the discrepancy between identified and unidentified bronchial asthma. Allergic rhinitis is correlated to, and constitutes a risk factor for the occurrence of complaints in the respiratory tract; public health policy should therefore be aimed at the prevention or early treatment of allergic rhinitis, and at reducing the proportion of cases suffering from unidentified bronchial asthma.


Differential efficacies of human type I and type II interferons as antiviral and antiproliferative agents.
Treatment of human fibroblast FS-4 cultures with human type II interferon preparations induced the synthesis of at least four proteins that were similar in size to four of the five proteins induced by type I interferons (Mr 120,000, 88,000, 67,000, and 56,000). However, the Mr 67,000 and 56,000 proteins were induced more strongly by type II than by type I interferon, and a counterpart of a Mr 80,000 protein induced by type I interferons was not noticeably induced by type II interferon preparations. We therefore compared type I and type II interferons for relative antiviral activities against different viruses (vesicular stomatitis, encephalomyocarditis, and vaccinia viruses and reovirus) and for cell growth-inhibitory activities on various cell types. The replication of vesicular stomatitis and encephalomyocarditis viruses was inhibited more strongly by type I interferon, whereas reovirus and vaccinia virus showed greater sensitivity to type II interferon preparations. This indicates that viruses may differ in their sensitivity to human type I and type II interferons and that the antiviral mechanisms induced by type I and type II interferons may have significant differences. The type I and type II interferons may have significant differences. The type I and type II interferons may also differ in their efficacies as antiproliferative agents. Type II interferon preparations at 2.5 units/ml inhibited the incorporatin of [3H]thymidine to a greater extent than did type I interferon at 400 units/ml. (For both type I and type II interferons, the unit of interferon activity was defined as the concentration that decreased the yield of vesicular stomatitis virus by 50% in FS-4 cultures.) Furthermore, whereas type II interferon preparations had a reversible cytostatic effect on normal human fibroblasts at 10 units/ml, the transformed cells tested (HeLa, osteosarcoma, U-amnion) showed extensive cell death, thus indicating that it may have a cytocidal effect on certain tumor cells. It appears that human type II interferon (or a factor present in these preparations) may be a potent antitumor agent.


Symptomless Multi-Variable Apnea Prediction Index Assesses Obstructive Sleep Apnea Risk and Adverse Outcomes in Elective Surgery.
To validate that the symptomless Multi-Variable Apnea Prediction index (sMVAP) is associated with Obstructive Sleep Apnea (OSA) diagnosis and assess the relationship between sMVAP and adverse outcomes in patients having elective surgery. We also compare associations between Bariatric surgery, where preoperative screening for OSA risk is mandatory, and non-Bariatric surgery groups who are not screened routinely for OSA. Using data from 40 432 elective inpatient surgeries, we used logistic regression to determine the relationship between sMVAP and previous OSA, current hypertension, and postoperative complications: extended length of stay (ELOS), intensive-care-unit-stay (ICU-stay), and respiratory complications (pulmonary embolism, acute respiratory distress syndrome, and/or aspiration pneumonia). Higher sMVAP was associated with increased likelihood of previous OSA, hypertension and all postoperative complications (p < .0001). The top sMVAP quintile had increased odds of postoperative complications compared to the bottom quintile. For ELOS, ICU-stay, and respiratory complications, respective odds ratios (95% CI) were: 1.83 (1.62, 2.07), 1.44 (1.32, 1.58), and 1.85 (1.37, 2.49). Compared against age-, gender- and BMI-matched patients having Bariatric surgery, sMVAP was more strongly associated with postoperative complications in non-Bariatric surgical groups, including: (1) ELOS (Orthopedics [p < .0001], Gastrointestinal [p = .024], Neurosurgery [p = .016], Spine [p = .016]); (2) ICU-stay (Orthopedics [p = .0004], Gastrointestinal [p < .0001], and Otorhinolaryngology [p = .0102]); and (3) respiratory complications (Orthopedics [p =.037] and Otorhinolaryngology [p =.011]). OSA risk measured by sMVAP correlates with higher risk for select postoperative complications. Associations are stronger for non-Bariatric surgeries, where preoperative screening for OSA is not routinely performed. Thus, preoperative screening may reduce OSA-related risk for adverse postoperative outcomes.


Effect of molar mass and alkyl chain length on the surface properties and biocompatibility of poly(alkylene terephthalate)s for potential cardiovascular applications.
Cardiovascular diseases are the leading cause of death worldwide. Treatments for occluded arteries include balloon angioplasty with or without stenting and bypass grafting surgery. Poly(ethylene terephthalate) is frequently used as a vascular graft material, but its high stiffness leads to compliance mismatch with the human blood vessels, resulting in altered hemodynamics, thrombus formation and graft failure. Poly(alkylene terephthalate)s (PATs) with longer alkyl chain lengths hold great potential for improving the compliance. In this work, the effect of the polymer molar mass and the alkyl chain length on the surface roughness and wettability of spin-coated PAT films was investigated, as well as the endothelial cell adhesion and proliferation on these samples. We found that surface roughness generally increases with increasing molar mass and alkyl chain length, while no trend for the wettability could be observed. All investigated PATs are non-cytotoxic and support endothelial cell adhesion and growth. For some PATs, the endothelial cells even reorganized into a tubular-like structure, suggesting angiogenic maturation. In conclusion, this research demonstrates the biocompatibility of PATs and their potential to be applied as materials serving cardiovascular applications.


An overview of countertransference with borderline patients.
Successful management of countertransference is critical to the psychotherapy of borderline patients. The author discusses the most common countertransference reactions encountered in such treatments. A theoretical framework is also proposed that conceptualizes countertransference as a joint creation between therapist and patient. It follows from this conceptual framework that therapists must constantly monitor their own contributions from past relationships as well as the aspects of countertransference evoked by the patient's behavior. Countertransference in the psychotherapy of borderline patients must be viewed as a source of valuable diagnostic and therapeutic information and not simply as interference with the therapeutic process.


Predicting 5-year risk of kidney transplant failure: a prediction instrument using data available at 1 year posttransplantation.
Accurate prediction of kidney transplant failure remains imperfect. The objective of this study was to develop and validate risk scores predicting 5-year transplant failure, based on data available 12 months posttransplantation. Development and then independent multicenter validation of risk scores predicting death-censored and overall transplant failure. Outcomes of kidney transplant recipients (n=651) alive with transplant function 12 months posttransplantation in Birmingham, United Kingdom, were used to develop models predicting transplant failure risk 5 years posttransplantation. The resulting risk scores were evaluated for prognostic utility (discrimination, calibration, and risk reclassification) in independent cohorts from Tours, France (n=736); Leeds, United Kingdom (n=787); and Halifax, Canada (n=475). Weighted regression coefficients for baseline and 12-month demographic and clinical predictor characteristics. Death-censored and overall transplant failure 5 years posttransplantation. Baseline data and time to transplant failure. Following model development, variables included in separate scores for death-censored and overall transplant failure included recipient age, sex, and race; acute rejection; transplant function; serum albumin level; and proteinuria. In the validation cohorts, these scores showed good to excellent discrimination for death-censored transplant failure (C statistics, 0.78-0.90) and moderate to good discrimination for overall transplant failure (C statistics, 0.75-0.81). Both scores demonstrated good calibration (Hosmer-Lemeshow P>0.05 in all cohorts). Compared with estimated glomerular filtration rate in isolation, application of the scores resulted in statistically significant and clinically relevant risk reclassification for death-censored transplant failure (net reclassification improvement [NRI], 36.1%-83.0%; all P<0.001) and overall transplant failure (NRI, 38.7%-53.5%; all P<0.001). Compared with the previously described US Renal Data System-based risk calculator, significant and relevant risk reclassification for overall transplant failure was seen (NRI, 30.0%; P<0.001). Validation is required in further populations. These validated risk scores may be of prognostic utility in kidney transplantation, accurately identifying at-risk transplants, and informing clinicians and patients.


Fracture resistance of posterior teeth restored with high-viscosity bulk-fill resin composites in comparison to the incremental placement technique.
Comparative evaluation of the fracture resistance of maxillary premolar teeth restored with two high-viscosity bulk-fill composites and incrementally placed composite. Seventy-five freshly extracted maxillary premolar teeth were selected. Fifteen specimens served as positive control (Group 1). Mesio-occluso-distal cavity preparation was prepared on the rest of the specimens. These specimens were further divided into four groups: unrestored teeth (Group 2), teeth restored with incrementally placed nanocomposite (Group 3), teeth restored with high-viscosity bulk-fill giomer (Group 4), and teeth restored with high-viscosity bulk-fill nanocomposite (Group 5). The specimens were then subjected to compressive axial load using Instron universal testing machine. Data were analyzed using data were analyzed using Statistical package for social sciences software (SPSS v 20.0, IBM Corp.). The positive control group exhibited highest fracture resistance (1104.70 ± 122.2 N). There was no statistically significant difference seen in between the incrementally placed nanocomposite and high-viscosity nanocomposite (P > 0.05). The fracture resistance values displayed by the high-viscosity bulk-fill giomer were found to be statistically lower than the other two groups. High-viscosity bulk-fill nanocomposite may substitute incrementally placed nanocomposite with respect to fracture resistance.


Vasodilator therapy in chronic asymptomatic aortic regurgitation: enalapril versus hydralazine therapy.
This study attempted to evaluate the long-term efficacy of enalapril versus hydralazine therapy on left ventricular volume, mass and function as well as on the renin-angiotensin system in chronic asymptomatic aortic regurgitation. We tested the hypothesis that early administration of a vasodilator drug might be able to reduce left ventricular dilation and mass expansion. Because the renin-angiotensin system may be activated in chronic aortic regurgitation, early enalapril therapy might be beneficial. Between 1990 and 1993, 76 asymptomatic nonrheumatic patients with mild to severe chronic aortic regurgitation were enrolled in a randomized, double-blind trial comparing enalapril with hydralazine. All patients underwent serial noninvasive studies. Seventy patients completed the 12-month follow-up. At 1 year, patients receiving enalapril had a significant reduction in left ventricular end-diastolic and end-systolic volume indexes (124 +/- 15 vs. 108 +/- 17 ml/m2, p < 0.01; 50 +/- 12 vs. 40 +/- 14 ml/m2, p < 0.01, respectively) and mass index (131 +/- 16 vs. 113 +/- 19 g/m2, p < 0.01), whereas hydralazine therapy showed no significant changes. Both regimens not only had a significant reduction in left ventricular mean wall stress but also had a mild increase in exercise duration. Only enalapril therapy achieved a significant inhibition of the renin-angiotensin system, in contrast to hydralazine therapy. Moreover, the multiple r2 value from the analysis for end-diastolic volume index using the two variables of age and treatment drugs was 72.1% (p < 0.01). Both regimens decrease left ventricular mean wall stress. Enalapril therapy achieves significant left ventricular mass regression, left ventricular end-diastolic and end-systolic volume index reduction and renin-angiotensin system suppression. These findings suggest that early unloading enalapril therapy has the potential to favorably influence the natural history of chronic aortic regurgitation.


The Marburg virus surface protein GP is phosphorylated at its ectodomain.
Marburg virus, a filovirus, contains only one transmembrane protein (GP) which is responsible for receptor recognition on target cells. GP, a type I membrane protein of approximately 220 kDa, is acylated and highly glycosylated carrying N- and O-linked sugar side chains. GP is transported through the exocytotic pathway toward the plasma membrane where budding of virions takes place. In the trans-Golgi network, GP is proteolytically activated by the prohormone convertase furin into two subunits GP(1) and GP(2). In the present paper, we provide evidence that GP undergoes an additional posttranslational modification; it is phosphorylated at its ectodomain. Phosphorylation takes place at serine residues between amino acid 260 and 273. The respective serines are located in conserved recognition sites for luminal protein kinases (protein kinase CK II and Golgi casein kinase). Consistent with this data, it was found that GP was phosphorylated in the Golgi apparatus of the expressing HeLa cells before cleavage of the molecule. GP is the first example of a viral glycoprotein with a phosphorylated ectodomain.


Decreased number and impaired function of type 1 regulatory T cells in autoimmune diseases.
Type 1 regulatory T (Tr1) cell is a special type of T regulatory cells with surface molecular markers such as lymphocyte-activation gene 3 and CD49b. A key property of Tr1 cells is the capability to produce high-level interleukin 10 (IL-10) upon activation, in a FOXP3-independent manner. The immunosuppressive function of IL-10 producing Tr1 cells has been extensively studied for many years. Autoimmune diseases (AIDs) are conditions in which the immune system breaks down and starts to attack the body. AIDs include inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis (MS), type 1 diabetes mellitus, Greaves' disease, and so forth. In recent years, more and more studies have documented that the number of Tr1 cells is decreased and the function is inhibited in a variety of AIDs, among which MS is the most widely studied. The protocol for engineering Tr1 cell therapy has been established and is gradually being used in clinical practice in recent years. Tr1 cell therapy has been proven to be safe and effective, but it is mainly involved in myeloid leukemia, graft versus host disease currently. Its therapeutic role in AIDs still needs to be further explored. In this study, we will summarize the research advances of Tr1 cells in AIDs, which will provide useful information for treating AIDs through Tr1 cell therapy in the future.


Hydrophilic interaction chromatography with a focus on the drug-phosphate interaction in drug screening to determine the phospholipidosis induction risk.
Cationic amphiphilic drugs (CADs) can induce the hyperaccumulation of phospholipids in cells and tissues. This side effect, which is known as drug-induced phospholipidosis, is sometimes problematic in the development and clinical use of CADs. It is known that CADs generally interact with phospholipids via both hydrophobic and acid-base interactions, and CADs with the larger affinity to phospholipid exhibit the larger induction risk. To develop a chromatographic assay system to predict the phospholipidosis-inducing potential with considering the acid-base interaction between CAD and phosphate group of phospholipid, hydrophilic interaction chromatographic (HILIC) methods were tested in this study. First, a PC HILIC column with phosphocholine groups on a packed material was used. The acid-base or other hydrophilic interactions to the stationary phase differed among basic drugs, and retention to the PC HILIC column did not accurately reflect the induction potential of phospholipidosis. As an alternative HILIC approach, the elution of CADs with the phosphate buffer from an amide column was tested. The elution effect, which is expressed as ratio of retention factors between different phosphate content in the mobile phase, closely correlated with the induction potential. Using the elution effect and retention factor to a reversed-phase HPLC column, the phospholipidosis-inducing drugs were clearly discriminated from the non-inducers. These results suggest that the proposed chromatographic approach can screen phospholipidosis-inducing drugs.


[The state of quality management implementation in ambulatory care nursing and inpatient nursing].
The demands being made on quality assurance and quality management in ambulatory care nursing and inpatient nursing facilities continue to grow. As opposed to health-care facilities such as hospitals and rehabilitation centres, we know of no other empirical studies addressing the current state of affairs in quality management in nursing institutions. The aim of this investigation was, by means of a questionnaire, to analyse the current (as of spring 2011) dissemination of quality management and certification in nursing facilities using a random sample as representative as possible of in- and outpatient institutions. To obtain our sample we compiled 800 inpatient and 800 outpatient facilities as a stratified random sample. Federal state, holder and, for inpatient facilities, the number of beds were used as stratification variables. 24% of the questionnaires were returned, giving us information on 188 outpatient and 220 inpatient institutions. While the distribution in the sample of outpatient institutions is equivalent to the population distribution, we observed discrepancies in the inpatient facilities sample. As they do not seem to be related to any demonstrable bias, we assume that our data are sufficiently representative. 4 of 5 of the responding facilities claim to employ their own quality management system, however the degree to which the quality management mechanisms are actually in use is an estimated 75%. Almost 90% of all the facilities have a quality management representative who often possesses specific additional qualifications. Many relevant quality management instruments (i. e., nursing standards of care, questionnaires, quality circles) are used in 75% of the responding institutions. Various factors in our data give the impression that quality management and certification efforts have made more progress in the inpatient facilities. Although 80% of the outpatient institutions claim to have a quality management system, only 32.1% of them admit to having already been (or be in current preparation to be) certified, a figure that was 41.5% among the inpatient facilities. These percentages are smaller when one relies on information provided by the certifying institutions themselves rather on the nursing facilities. Most frequent is the certification according to the DIN EN ISO 9001 standard, since the care-specific certification procedures most widespread on the market enable facilities to combine a care-specific certificate with one according to DIN norms. Quality management has become very widespread in nursing facilities: every third institution claims to have been certified, and the trend to become certified has clearly intensified over the last few years. We observe overall very great acceptance of both internal quality management and external quality assurance. We suspect that the current use of quality management instruments in many nursing facilities will not fall behind such efforts in hospitals and rehabilitation centres.


Leclercia adecarboxylata Bacteremia in a Patient with Ulcerative Colitis.
Patients with inflammatory bowel disease (IBD) are a high risk population for bacteremia. Derangement in the mucosal architecture of the gastrointestinal (GI) tract and frequent endoscopic interventions in immunocompromised individuals are considered primary causes. Isolation of opportunistic microorganisms from the bloodstream of IBD patients has been increasingly reported in recent years. Leclercia adecarboxylata is a ubiquitous, aerobic, motile, gram-negative bacillus. The human GI tract is known to harbor this rarely pathogenic microorganism. There are only a few case reports of bacteremia with this microorganism; the majority are either polymicrobial or associated with immunocompromised patients. We describe a case of monomicrobial L. adecarboxylata bacteremia in a 43-year-old female who presented with bloody diarrhea. Colonoscopy revealed diffuse colonic mucosal inflammation with numerous ulcers, and histopathology revealed crypt abscesses. Following an episode of rectal bleeding, two sets of blood cultures grew L. adecarboxylata, which was treated with intravenous ceftriaxone. After a complicated hospital course, she was eventually diagnosed with ulcerative colitis and enteropathic arthritis, treated with intravenous methylprednisolone, mesalamine, and infliximab which resulted in resolution of her symptoms. In our previously immunocompetent patient, derangement of the gut mucosal barrier was the likely cause of bacteremia, yet performing endoscopic intervention may have contributed to bacterial translocation.


Coral larvae are poor swimmers and require fine-scale reef structure to settle.
Reef coral assemblages are highly dynamic and subject to repeated disturbances, which are predicted to increase in response to climate change. Consequently there is an urgent need to improve our understanding of the mechanisms underlying different recovery scenarios. Recent work has demonstrated that reef structural complexity can facilitate coral recovery, but the mechanism remains unclear. Similarly, experiments suggest that coral larvae can distinguish between the water from healthy and degraded reefs, however, whether or not they can use these cues to navigate to healthy reefs is an open question. Here, we use a meta-analytic approach to document that coral larval swimming speeds are orders of magnitude lower than measurements of water flow both on and off reefs. Therefore, the ability of coral larvae to navigate to reefs while in the open-ocean, or to settlement sites while on reefs is extremely limited. We then show experimentally that turbulence generated by fine scale structure is required to deliver larvae to the substratum even in conditions mimicking calm back-reef flow environments. We conclude that structural complexity at a number of scales assists coral recovery by facilitating both the delivery of coral larvae to the substratum and settlement.


Antiviral signaling through pattern recognition receptors.
Viral infection is detected by the host innate immune system. Innate immune cells such as dendritic cells and macrophages detect nucleic acids derived from viruses through pattern recognition receptors (PRRs). Viral recognition by PRRs initiates the activation of signaling pathways that lead to production of type I interferon and inflammatory cytokines, which are important for the elimination of viruses. Two types of PRRs that recognize viral nucleic acids, Toll-like receptors (TLR) and RIG-I-like RNA helicases (RLH), have been identified. Of the TLRs, TLR3 recognizes viral double-stranded (ds) RNA, TLR7 and human TLR8 identify viral single-stranded (ss) RNA and TLR9 detects viral DNA. TLRs are located in endosomal compartments, whereas RLH are present in the cytoplasm where they detect viral dsRNA or ssRNA. Here we review the role of TLRs and RLHs in the antiviral innate immune response.


13C-NMR, 1H-NMR and gas-chromatography mass-spectrometry studies of the biosynthesis of 13C-enriched L-lysine by Brevibacterium flavum.
The basic metabolic pathways of lysine biosynthesis in Brevibacterium flavum, a strain which excretes excessive amounts of L-lysine, have been followed by using two 13C-labeled precursors. 13C- and 1H-NMR spectroscopies in conjunction with gas chromatography mass spectrometry (GC-MS) have revealed the various metabolic pathways leading to L-[13C]lysine. Discrete metabolic pathways give rise to distinct labeling patterns. L-Lysine resulting from [1-13C]glucose fermentation is relatively specifically labeled: L-[3,5-13C]lysine is the main product. Experimental and theoretical approaches based on the 13C-enrichment values of intracellular glutamate, a major intermediate metabolite, allowed us to assess the relative contribution of the major metabolic pathways forming lysine. The labeling pattern of glutamate reflects the isotope distribution in 2-oxoglutarate. When [2-13C]acetate is used as the sole carbon source in the culture, the energy-producing steps of the Krebs cycle are essential. The higher activity of the Krebs cycle, when endogenous carbohydrates are exhausted from the culture, is indicated by the increased 13C enrichment in C-1 of lysine and reveal a high content of isotopomers of four, five and six 13C atoms in the lysine molecule, pointing out that the four-carbon intermediates of the cycle are being derived from the glyoxylate shunt pathway. Such a phenomenon does not occur in glucose fermentation. GC-MS analyses of 13C enrichments and isotopomer distributions in metabolites and end products are in good agreement with the predicted contribution of each metabolic pathway. This new methodological approach of combined NMR and GC-MS has been demonstrated to be applicable to various other metabolic studies.


Sex-related differences in reproductive allocation, growth, defense and herbivory in three dioecious neotropical palms.
Frequently, in dioecious plants, female plants allocate more resources to reproduction than male plants. Therefore it is expected that asymmetrical allocation to reproduction may lead to a reproduction-growth tradeoff, whereby female plants grow less than male plants, but invest more in defenses and thus experience lower herbivory than male plants. We tested these expectations by comparing resource allocation to reproduction, growth and defense and its consequences on herbivory in three sympatric dioecious Chamaedorea palms (C. alternans, C. pinnatifrons and C. ernesti-augusti) using a pair-wise design (replicated male/female neighboring plants) in a Mexican tropical rain forest. Our findings support the predictions. Biomass allocation to reproduction in C. pinnatifrons was 3-times higher in female than male plants, consistent with what is known in C. alternans and C. ernesti-augusti. Growth (height and leaf production rate and biomass production) was higher in male plants of all three species. Female plants of the three species had traits that suggest greater investment in defense, as they had 4-16% tougher leaves, and 8-18% higher total phenolic compounds concentration. Accordingly, female plants sustained 53-78% lower standing herbivory and 49-87% lower herbivory rates than male plants. Our results suggests that resource allocation to reproduction in the studied palms is more costly to female plants and this leads to predictable intersexual differences in growth, defense and herbivory. We conclude that resource allocation to reproduction in plants can have important consequences that influence their interaction with herbivores. Since herbivory is recognized as an important selective force in plants, these results are of significance to our understanding of plant defense evolution.


Exploring the Role of Enhancer-Mediated Transcriptional Regulation in Precision Biology.
The emergence of precision biology has been driven by the development of advanced technologies and techniques in high-resolution biological research systems. Enhancer-mediated transcriptional regulation, a complex network of gene expression and regulation in eukaryotes, has attracted significant attention as a promising avenue for investigating the underlying mechanisms of biological processes and diseases. To address biological problems with precision, large amounts of data, functional information, and research on the mechanisms of action of biological molecules is required to address biological problems with precision. Enhancers, including typical enhancers and super enhancers, play a crucial role in gene expression and regulation within this network. The identification and targeting of disease-associated enhancers hold the potential to advance precision medicine. In this review, we present the concepts, progress, importance, and challenges in precision biology, transcription regulation, and enhancers. Furthermore, we propose a model of transcriptional regulation for multi-enhancers and provide examples of their mechanisms in mammalian cells, thereby enhancing our understanding of how enhancers achieve precise regulation of gene expression in life processes. Precision biology holds promise in providing new tools and platforms for discovering insights into gene expression and disease occurrence, ultimately benefiting individuals and society as a whole.


Effects of ginseng and echinacea on cytokine mRNA expression in rats.
The aim of the study was to determine the effect of ginseng and echinacea on the mRNA expression of IL-10, TNF-α, and TGF-β1 in healthy rats. Six-week-old male Fischer 344 rats (n = 48) were used. The animals were divided into three equal groups, as follows: control (C); ginseng (G); echinacea (E). While the C group was fed a standard rat diet (Purina) ad libitum for a period of 40 days, the G and E groups animals received the same diet containing 0.5 g/kg of Panax ginseng root powder and 0.75 g/kg of Echinacea purpurea root powder, respectively. Blood samples were obtained from 8 rats in each group after 20 and 40 days of treatment, and the mRNA expression of IL-10, TNF-α, and TGF-β1 was determined. After 20 days of treatment, the expression of IL-10 mRNA in the G group was different from the C group (P < 0.05); however, after 40 days of treatment, there was no difference between the groups. There was no difference after 20 and 40 days of treatment between the groups with respect to the expression of TGF-β1 mRNA. After 20 days of treatment, the expression of TNF-α mRNA in the E group was higher (P < 0.05) than the C group. After 40 days of treatment, the expression of TNF-α mRNA was similar in all of the groups. Based on the current study, the increase in expression of IL-10 mRNA in the G group and the increase in expression of TNF-α mRNA in the E group support the use of these plants for purposes of modulating the immune system. However, a more detailed study regarding the effects of ginseng and echinacea on these cytokines and other cytokines is needed.


[Characteristics of the fatal outcome of drug-induced anaphylactic shock].
Among 520 cases of drug anaphylactic shock there were 48 (9.2%) fatal outcomes. Analysis of the pathomorphological changes in shock showed them to have characteristic features consisting in blood redistribution (decentralization), its deposition in parenchymatous organs with marked disorders in microcirculation and diapedetic hemorrhages in serous, mucous membranes, and tissue of nearly all the organs, as well as signs of stasis and leukocyte aggregation, perivascular and pericellular edema and swelling of cells of different organs. In a protracted course of shock, marked degenerative changes of parenchymatous organs were observed. In the acute course and rapid fatal outcome pathomorphological changes were less marked than in a protracted and recurrent course which was characterized by the development of secondary pathological changes such as inflammatory, degenerative, and necrotic processes.


Technetium-99m RBC scintigraphy in the evaluation of small bowel leiomyoma.
Hypervascularity and persistent uptake were demonstrated in a small bowel leiomyoma not actively bleeding at the time of Tc-99m RBC scintigraphy. The potential value of Tc-99m RBC scanning in the evaluation of benign small bowel tumors is discussed.


Survival advantage of peritoneal dialysis relative to hemodialysis in the early period of incident dialysis patients: a nationwide prospective propensity-matched study in Korea.
The impact of dialysis modality on survival is still somewhat controversial. Given possible differences in patients' characteristics and the cause and rate of death in different countries, the issue needs to be evaluated in Korean cohorts. A nationwide prospective observational cohort study (NCT00931970) was performed to compare survival between peritoneal dialysis (PD) and hemodialysis (HD). A total of 1,060 end-stage renal disease patients in Korea who began dialysis between September 1, 2008 and June 30, 2011 were followed through December 31, 2011. The patients (PD, 30.6%; HD, 69.4%) were followed up for 16.3 ± 7.9 months. PD patients were significantly younger, less likely to be diabetic, with lower body mass index, and larger urinary volume than HD patients. Infection was the most common cause of death. Multivariate Cox regression with the entire cohort revealed that PD tended to be associated with a lower risk of death compared to HD [hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.36-1.08]. In propensity score matched pairs (n=278 in each modality), cumulative survival probabilities for PD and HD patients were 96.9% and 94.1% at 12 months (P=0.152) and 94.3% and 87.6% at 24 months (P=0.022), respectively. Patients on PD had a 51% lower risk of death compared to those on HD (HR 0.49, 95% CI 0.25-0.97). PD exhibits superior survival to HD in the early period of dialysis, even after adjusting for differences in the patients' characteristics between the two modalities. Notably, the most common cause of death was infection in this Korean cohort.


Conversion of stationary to invasive tumor initiating cells (TICs): role of hypoxia in membrane type 1-matrix metalloproteinase (MT1-MMP) trafficking.
Emerging evidence has implicated the role of tumor initiating cells (TICs) in the process of cancer metastasis. The mechanism underlying the conversion of TICs from stationary to invasive remains to be characterized. In this report, we employed less invasive breast cancer TICs, SK-3rd, that displays CD44(high)/CD24(low) with high mammosphere-forming and tumorigenic capacities, to investigate the mechanism by which stationary TICs are converted to invasive TICs. Invasive ability of SK-3rd TICs was markedly enhanced when the cells were cultured under hypoxic conditions. Given the role of membrane type 1-matrix metalloproteinase (MT1-MMP) in cancer invasion/metastasis, we explored a possible involvement of MT1-MMP in hypoxia-induced TIC invasion. Silencing of MT1-MMP by a shRNA approach resulted in diminution of hypoxia-induced cell invasion in vitro and metastasis in vivo. Under hypoxic conditions, MT1-MMP redistributed from cytoplasmic storage pools to the cell surface of TICs, which coincides with the increased cell invasion. In addition, CD44, a cancer stem-like cell marker, inversely correlated with increased cell surface MT1-MMP. Interestingly, cell surface MT1-MMP gradually disappeared when the hypoxia-treated cells were switched to normoxia, suggesting the plasticity of TICs in response to oxygen content. Furthermore, we dissected the pathways leading to upregulated MT1-MMP in cytoplasmic storage pools under normoxic conditions, by demonstrating a cascade involving Twist1-miR10b-HoxD10 leading to enhanced MT1-MMP expression in SK-3rd TICs. These observations suggest that MT1-MMP is a key molecule capable of executing conversion of stationary TICs to invasive TICs under hypoxic conditions and thereby controlling metastasis.


Antibody-induced redistribution of CEA on the cell surface: utilization in separation of CEA and isoantigen A.
Antibodies specific for carcinoembryonic antigen (CEA) induced polar redistribution of CEA which was expressed on the surface of human intestinal carcinoma cells grown in tissue culture. Polar redistribution occurred at 23 degrees C and 37 degrees C but not at 4 degrees C and was inhibited by sodium azide and cytochalasin B. Antibodies to isoantigen A did not react with CEA at the cell surface but did react with isoantigen A which was not redistributed by the antibody. Cells which expressed both CEA and isoantigen A were used to demonstrate that polar redistribution of CEA could be induced without altering the distribution of isoantigen A. The data indicate that CEA and isoantigen A can be expressed on the same cell as separate molecules.


Modified finger exercise board.
This article describes constructional and material changes made to a finger exercise board (1), a device that provides the occupational therapist with versatile equipment for resistive exercises for most muscles of the hand. It is particularly effective in the treatment of disabilities that involve multiple muscles of the hand such as is commonly the case in rheumatoid arthritis. The modifications of the board have substantially eased grading resistive tension, and construction has been simplified and its stability increased. Brief additional information is supplied below for use of the exercise board in the treatment of arthritic deformities.


Coated minispheres of salmon calcitonin target rat intestinal regions to achieve systemic bioavailability: Comparison between intestinal instillation and oral gavage.
Achieving oral peptide delivery is an elusive challenge. Emulsion-based minispheres of salmon calcitonin (sCT) were synthesized using single multiple pill (SmPill®) technology incorporating the permeation enhancers (PEs): sodium taurodeoxycholate (NaTDC), sodium caprate (C10), or coco-glucoside (CG), or the pH acidifier, citric acid (CA). Minispheres were coated with an outer layer of Eudragit® L30 D-55 (designed for jejunal release) or Surelease®/Pectin (designed for colonic release). The process was mild and in vitro biological activity of sCT was retained upon release from minispheres stored up to 4months. In vitro release profiles suggested that sCT was released from minispheres by diffusion through coatings due to swelling of gelatin and the polymeric matrix upon contact with PBS at pH6.8. X-ray analysis confirmed that coated minispheres dissolved at the intended intestinal region of rats following oral gavage. Uncoated minispheres at a dose of ~2000I.U.sCT/kg were administered to rats by intra-jejunal (i.j.) or intra-colonic (i.c.) instillation and caused hypocalcaemia. Notable sCT absolute bioavailability (F) values were: 5.5% from minispheres containing NaTDC (i.j), 17.3% with CG (i.c.) and 18.2% with C10 (i.c.). Coated minispheres administered by oral gavage at threefold higher doses also induced hypocalcaemia. A highly competitive F value of 2.7% was obtained for orally-administered sCT-minispheres containing CG (45μmol/kg) and coated with Eudragit®. In conclusion, the SmPill® technology is a potential dosage form for several peptides when formulated with PEs and coated for regional delivery. PK data from instillations over-estimates oral bioavailability and poorly predicts rank ordering of formulations.


The antigenicity and cholesteroid nature of mycolic acids determined by recombinant chicken antibodies.
Mycolic acids (MA) are major, species-specific lipid components of Mycobacteria and related genera. In Mycobacterium tuberculosis, it is made up of alpha-, methoxy- and keto-MA, each with specific biological functions and conformational characteristics. Antibodies in tuberculosis (TB) patient sera respond differently towards the three MA classes and were reported to cross-react with cholesterol. To understand the antigenicity and cholesterol cross-reactivity of MA, we generated three different chicken -derived phage-displayed single-chain variable fragments (scFv) that reacted similarly towards the natural mixture of MA, but the first recognized all three classes of chemically synthetic MAs, the second only the two oxygenated types of MAs and the third only methoxy MA. The cholesterol cross-reactivity was investigated after grafting each of the three scFv types onto two configurations of constant chain domains-CH1-4 and CH2-4. Weak but significant cross-reactivity with cholesterol was found only with CH2-4 versions, notably those two that were also able to recognize the trans-keto MA. The cholesteroid nature of mycobacterial mycolic acids therefore seems to be determined by the trans-keto MA subclass. The significantly weaker binding to cholesterol in comparison to MA confirms the potential TB diagnostic application of these antibodies.


Adjunctive buccal and palatal corticotomy for adult maxillary expansion in an animal model.
This study aimed to explore the usefulness of adjunctive buccal and palatal corticotomy for adult maxillary expansion in an animal model using cone-beam computed tomography (CBCT). Twelve adult sheep were randomly divided into two groups (each n = 6): a control group, where no treatment was administered, and a treatment group, where buccal and palatal corticotomy-assisted maxillary expansion was performed. CBCT scans were taken before (T1) and after (T2) treatment. Differences in all transverse dental and alveolar dimensions, alveolar width at crest level, hard palate level, horizontal bone loss, interdental cusp width and inter-root apex were assessed using Wilcoxon signed-rank and Mann-Whitney U-tests. Kruskal-Wallis tests and pairwise comparisons were used to detect the significance of differences among the inter-premolar and inter-molar widths. CBCT data revealed significant changes in all transverse dental and alveolar dimensions. The mean interpremolar alveolar width showed an increase of 2.29 to 3.62 mm at the hard palate level, 3.89 to 4.38 mm at the alveolar crest level, and 9.17 to 10.42 mm at the buccal cusp level. Dental changes in the vertical dimension were not significant. Our findings based on an adult animal model suggest that adjunctive buccal and palatal corticotomy can allow for both skeletal and dental expansion, with the amount of dental expansion exceeding that of skeletal expansion at alveolar crest and hard palate levels by two and three folds, respectively. Therefore, this treatment modality is potential to enhance the outcomes of maxillary expansion in adults.


Euthanasia and physician-assisted suicide among patients with amyotrophic lateral sclerosis in the Netherlands.
Amyotrophic lateral sclerosis (ALS) is a disease that causes progressive paralysis leading to respiratory failure. Patients with ALS may consider physician-assisted suicide. However, it is not known how many patients, if given the option, would actually decide to end their lives by physician-assisted suicide or euthanasia nor at what stage of the disease they would choose to do so. We identified physicians of 279 patients in the Netherlands with a diagnosis of ALS who died between 1994 and 1999. Physicians were asked to fill out a validated questionnaire about the end-of-life decisions that were made. Of 241 eligible physicians, 203 returned the questionnaire (84 percent). Of the 203 patients, 35 (17 percent) chose euthanasia and died that way. An additional six patients (3 percent) died as a result of physician-assisted suicide. Patients to whom religion was important were less likely to have died as a result of euthanasia or physician-assisted suicide. The choice of euthanasia or physician-assisted suicide was not associated with any particular characteristics of the disease or of the patient's care, nor was it associated with income or educational level. Disability before death was significantly more severe in patients who died as a result of euthanasia than among those who died in other ways. Physician-assisted suicide appeared to occur somewhat earlier in the course of the disease than did euthanasia. An additional 48 patients (24 percent) received palliative treatment, which probably shortened their lives. In the Netherlands, we found that one in five patients with ALS died as a result of euthanasia or physician-assisted suicide.


Percutaneous treatment of simple renal cysts with 24-h-interval ethanol sclerotherapy.
To investigate the efficacy of 24-h interval multiple-session ethanol sclerotherapy for the treatment of simple renal cysts. The study sample included 58 patients (mean age, 65.37 ± 11.95 years). We included 76 simple renal cysts that were treated with percutaneous aspiration with a minimum of two sessions of 95% ethanol sclerotherapy in a 24-h interval between sessions. Patients were evaluated at 1, 3, and 6 months after the intervention for the efficacy of the treatment. Treatment success was defined as a complete regression of a cyst or a > 50% reduction in its volume, with no recurrence of symptoms. The mean preprocedural cyst size was 72.98 ± 25.14 mm, and the mean preprocedural cyst volume was 205.76 ± 244.15 mL. The mean volume of ethanol used in the first sclerotherapy session was 62.76 ± 30.71 mL. The mean fluid accumulation in the cysts at the end of the first 24-h interval was 4.66 ± 7.13 mL. The mean quantity of ethanol used in the second sclerotherapy session was 26.48 ± 22.2 mL. A third sclerotherapy session was required in only 10 (13.2%) of the cysts. The mean follow-up period was 52.84 ± 37.83 months. The rate of complete regression was 97.4% for the whole sample at the end of the follow-up. Ethanol ablation with 24-h intervals is a safe and effective treatment option in the minimally invasive percutaneous treatment of simple renal cysts.


Update on pathogenesis and treatment of CLE.
Cutaneous Lupus Erythematous (CLE) is an autoimmune disease in which patients may present with isolated skin findings or have CLE associated with underlying systemic disease. The most significant recent studies on its pathogenesis and therapeutic management are reviewed here. Patients with subacute and Discoid Lupus Erythematous had elevated Interferon score, about a third of all cases of SCLE could be attributed to previous drug exposure, and smoking may be more closely associated with CLE than Systemic Lupus Erythematous (SLE). An underlying genetic defect in some subsets of CLE patients may also be shared with SLE. Efficacy of antimalarial therapy is enhanced by increasing treatment duration or maintaining higher blood drug concentrations. Combination antimalarials that include quinacrine, thalidomide analogs, and Mycophenalate Mofetil may also be effective in refractory CLE. The pathogenesis of CLE remains unclear, and is likely multifactorial. Identified associations with subsets of CLE suggest future research questions in CLE pathogenesis. Subsets of CLE associated with interface dermatitis may share an underlying genetic defect in interferon signaling with SLE. The Cutaneous Lupus Disease Area and Severity Index is a valuable and widely used tool allowing standardized assessment and reporting of cutaneous disease activity and damage. More evidence is available to guide treatment of refractory CLE, but larger studies are needed. http://links.lww.com/COR/A4.


Functional CD2 mutants unable to bind to, or be stimulated by, LFA-3.
To define epitopes on the CD2 (T11, the T cell erythrocyte receptor) molecule that are necessary for interaction with lymphocyte function-associated Ag-3 (LFA-3), we have expressed the human wild-type CD2 cDNA and mutant CD2 cDNA in a murine Ag-specific T cell hybridoma that responds to human HLA-DR Ag. Here we have expressed mutations at amino acid 91 and 92 of CD2 in the T cell hybridoma. The mutated CD2 molecules were functional in that pairs of anti-CD2 mAb that continued to bind were able to stimulate IL-2 production by the hybridomas. However, CD2 mutants with either the 91 or 92 amino acid substitution had lost the ability to bind to or be activated by either SRBC, which bear an LFA-3 homologue, or by murine L cells expressing human LFA-3. Unlike hybridomas expressing the wild-type CD2 molecule, there was no enhanced response to Ag stimulation. Taken together, these data suggest that the mutated CD2 molecules were no longer able to bind to, or to utilize, LFA-3 for activation. We have previously demonstrated that a mutation at amino acid 51 of CD2 results in loss of binding to LFA-3. Whether these two regions of CD2, discrete and separable by amino acid sequence, form one or more binding sites for LFA-3 remains to be determined.


Cloning and Functional Characterization of a Pericarp Abundant Expression Promoter (AhGLP17-1P) From Peanut (Arachis hypogaea L.).
Peanut (Arachis hypogaea L.) is an important oil and food legume crop grown in tropical and subtropical areas of the world. As a geocarpic crop, it is affected by many soil-borne diseases and pathogens. The pericarp, an inedible part of the seed, acts as the first layer of defense against biotic and abiotic stresses. Pericarp promoters could drive the defense-related genes specific expression in pericarp for the defense application. Here, we identified a pericarp-abundant promoter (AhGLP17-1P) through microarray and transcriptome analysis. Besides the core promoter elements, several other important cis-elements were identified using online promoter analysis tools. Semiquantitative and qRT-PCR analyses validated that the AhGLP17-1 gene was specifically expressed only in the pericarp, and no expression was detected in leaves, stem, roots, flowers, gynophore/peg, testa, and embryo in peanut. Transgenic Arabidopsis plants showed strong GUS expression in siliques, while GUS staining was almost absent in remaining tissues, including roots, seedlings, leaf, stem, flowers, cotyledons, embryo, and seed coat confirmed its peanut expressions. Quantitative expression of the GUS gene also supported the GUS staining results. The results strongly suggest that this promoter can drive foreign genes' expression in a pericarp-abundant manner. This is the first study on the functional characterization of the pericarp-abundant promoters in peanut. The results could provide practical significance to improve the resistance of peanut, and other crops for seed protection uses.


Direct-cortical visual evoked potential monitoring during brain tumor resection.
Visual evoked potential (VEP) recording is traditionally regarded as an unreliable evoked potential monitoring technique, precluding widespread use in intracranial neurosurgery. However, VEPs can serve as a useful intraoperative adjunct for real-time detection of mechanical damage to optic apparatuses. The low obtainability and prognostic utility of VEPs are associated with transcranial recording, which typically provides non-focal information and poor signal-to-noise ratio. Direct cortical VEP (DC-VEP) recordings may offer a solution. We evaluated the obtainability of DC-VEPs as well as their prognostic utility in predicting postoperative visual function deterioration in a series of brain tumor patients undergoing craniotomies for tumor resection. Patient records were retrospectively reviewed for all consecutive patients undergoing brain tumor resections with DC-VEP monitoring. Pre- and postoperative visual fields were characterized from patient charts and associated with the presence of intraoperative monitoring alerts to determine the sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of DC-VEPs in detecting postoperative visual field deficits. Twenty-two patients (9 male, 13 female) were included, with a median age of 60 years. DC-VEPs were reliably detected in 19 of 23 included surgeries (82.6%). The reported sensitivity, specificity, PPV, and NPV in detecting postoperative visual field deficits was 60%, 92.9%, 75%, and 86.7%, respectively. There was a statistically significant association between monitoring alerts and the presence of visual field deterioration by Fischer's exact test (p = 0.0374). DC-VEPs can be reliably obtained and are useful for detecting mechanical injury to optic areas and tracts during tumor resection.


Prevalence of Psychosocial and Behavioral Aspects in Victims of Motorcycle Accidents in Civil Hospital, Karachi.
Introduction Motorcycles are common in a developing nation like Pakistan. In addition to their benefits, motorcycles carry a high risk for accident and injury. Many factors can exacerbate the risk of motorcycle operation including the use of mobile phones while riding, a lack of knowledge of traffic rules, not following road rules or non-satisfactory vehicle health and road conditions. Along with these physical factors, some psychosocial aspects also impact risks, including aggressive behavior of drivers or variations in driving patterns associated with changes in driver mood. Objective We conducted this study to determine the association of rider/operator behavioral and psychosocial factors with motor vehicle crashes. Methods We conducted a cross-sectional study on the patients of Civil Hospital in Karachi, Pakistan aged between 15 to 65 years. Data were collected from 150 patients in the outpatient department and emergency room via a questionnaire assessing driver biodata, license details, socioeconomic status, and their behavioral and psychosocial conditions. Inclusion criteria were limited to patients with motorcycle accidents only; patients involved in accidents from any other form of vehicle were excluded. Result Of the 150 patients, 70% were reported varying their driving speed with fluctuating moods, 80% rode aggressively when they have any social or financial issue, and 57% became annoyed with another driver's behavior-all of which highlight the influence of psychosocial factors in motorcycle crashes. Concerning behavioral factors, 88% of drivers were involved in unofficial races, 44% reported overtaking slower drivers, and 80% violated traffic signals on a regular basis. These results suggest that behavioral and psychosocial factors have a major influence on the victims of motorcycle accidents and are an important cause of injury due to crashes. Conclusion Psychosocial and behavior aspects play a critical role in motorcycle accidents. Riders experiencing family-related or social-related stress and those with an aggressive personality are more prone to have a motorcycle accident than riders who do not have those stressors. Additional measures should be taken to raise awareness regarding these important contributing factors, including stress management in driving education.


Vancomycin therapeutic drug monitoring: is it necessary?
To review the literature and assess the validity of obtaining vancomycin serum drug concentrations in patients. A MEDLINE search of the English literature and a bibliographic review of articles pertaining to vancomycin serum concentrations, their use, and the rationale of cited therapeutic ranges. Studies pertaining to the use of vancomycin concentrations in the clinical setting, methods for predicting these concentrations, and studies that reported efficacy or toxicity associated with vancomycin use and possible correlation of serum concentrations. The usefulness of vancomycin serum concentrations, the determination of a therapeutic range of values, and their correlation to antibacterial efficacy and drug toxicity in the clinical setting are controversial. Old reports of toxicities need to be critically examined due to lack of information and the actual frequency of toxic reactions. The efficacy of vancomycin's antibacterial effect and its correlation with reported therapeutic ranges may advocate obtaining a vancomycin trough concentration in certain groups of patients. Determination of serum vancomycin concentrations in the clinical setting and their usefulness in patient care is questionable and unnecessary in the majority of patients.


Adolescent Pathways to Co-Occurring Problem Behavior: The Effects of Peer Delinquency and Peer Substance Use.
Delinquency and substance use are more likely to co-occur in adolescence compared to earlier and later developmental periods. The present study examined developmental pathways to co-occurring problem behavior from 6th-10th grade (N=2,002), testing how peer delinquency and substance use were linked to transitioning between abstaining, delinquency, substance use, and co-occurring problem behavior. Developmentally, most youth transition from abstinence to delinquent behavior, and then escalate to co-occurring problem behavior. Once co-occurring problem behavior onsets, remitting to single problem behavior or abstinence is unlikely. The impact of peers on problem behavior are domain specific when individuals transition from abstaining to a single problem behavior, but are more general with respect to escalation of and desistance from problem behavior.